A Phase 1a/1b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY159 as a Single Agent and In Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 127
- 试验地点
- 17
- 主要终点
- Dose Limiting Toxicity of PY159 (Part A only)
研究概览
简要总结
This is an open-label, multicenter, First-In-Human (FIH), Phase 1a/1b study of PY159 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to Standard Of Care (including Checkpoint Inhibitors, if approved for that indication).
详细描述
Part A: Dose escalation of PY159 alone and in combination with pembrolizumab in a standard 3+3 design Part B: Dose expansion of one or more dose levels of PY159 administered alone and in combination with pembrolizumab for predefined tumor histology
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: PY159 Single agent dose level 1
PY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision.
干预措施: PY159 Single agent dose level 1 (Drug)
Part A: PY159 Single agent dose level 2
PY159 dose level 2
干预措施: PY159 Single agent dose level 2 (Drug)
Part A: PY159 single agent dose level 3
PY159 dose level 3
干预措施: PY159 Single agent dose level 3 (Drug)
Part A: PY159 single agent dose level 4
PY159 dose level 4
干预措施: PY159 Single agent dose level 4 (Drug)
Part A: PY159 single agent dose level 5
PY159 dose level 5
干预措施: PY159 Single agent dose level 5 (Drug)
Part A: PY159 single agent dose level 6
PY159 dose level 6
干预措施: PY159 Single agent dose level 6 (Drug)
Part A: PY159 single agent dose level 7
PY159 dose level 7
干预措施: PY159 Single agent dose level 7 (Drug)
Part A: PY159/Pembrolizumab Combination dose level 1
PY159 dose level 1 in combination with pembrolizumab
干预措施: PY159/Pembrolizumab Combination dose level 1 (Drug)
Part A: PY159/Pembrolizumab Combination dose level 2
PY159 dose level 2 in combination with pembrolizumab
干预措施: PY159/Pembrolizumab Combination dose level 2 (Drug)
Part A: PY159/Pembrolizumab Combination dose level 3
PY159 dose level 3 in combination with pembrolizumab
干预措施: PY159/Pembrolizumab Combination dose level 3 (Drug)
Part A: PY159/Pembrolizumab Combination dose level 4
PY159 dose level 4 in combination with pembrolizumab
干预措施: PY159/Pembrolizumab Combination dose level 4 (Drug)
PY159 Part B: Single agent dose expansion cohort(s)
PY159 Single agent dose expansion cohort(s)
干预措施: PY159 Single agent dose expansion cohort (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1
PY159 in combination with pembrolizumab dose expansion cohort 1 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 1 (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 2
PY159 in combination with pembrolizumab dose expansion cohort 2 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 2 (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 3
PY159 in combination with pembrolizumab dose expansion cohort 3 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 3 (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4
PY159 in combination with pembrolizumab dose expansion cohort 4 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 4 (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 5
PY159 in combination with pembrolizumab dose expansion cohort 5 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 5 (Drug)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6
PY159 in combination with pembrolizumab dose expansion cohort 6 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
干预措施: PY159/Pembrolizumab Combination dose expansion cohort 6 (Drug)
结局指标
主要结局
Dose Limiting Toxicity of PY159 (Part A only)
时间窗: 21 days
Evaluation of dose-limiting toxicity (DLT).
Incidence of Adverse Events (AE)
时间窗: 36 months
Adverse Events will be summarized by MedDRA system organ class and preferred term. Separate tabulations will be produced for all treatment emergent AEs, treatment related AEs, Serious Adverse Events (SAEs), discontinuations due to AEs, and AEs of at least NCI CTCAE grade 3 severity.
次要结局
- Measure PY159 concentration at the end of infusion (CEOI)(36 months)
- Measure PY159 maximum concentration (Cmax)(36 months)
- Measure PY159 concentration at the trough level (Ctrough)(36 months)
- Measure PY159 Clearance (CL)(36 months)
- Measure PY159 Volume at Steady State (Vss)(36 months)
- Measure PY159 Area under the curve (AUC)0-t(36 months)
- Measure PY159 half-life (T1/2)(36 months)
- Incidence of Anti-Drug Antibody (ADA) formation to PY159(36 months)
- Determining PY159 time to maximum concentration (Tmax)(36 months)
- Objective response rate (ORR)(36 months)
- Clinical Benefit Rate (CBR)(36 months)
- Duration of response (DOR)(36 months)